Continuous production of hyaluronic acids is a key trigger to cancer initiation, growth

by Alan Flurry
Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology, co-authored a study that found that low oxygen levels could be a key driver of cancer growth.

(Medical Xpress)—Chronic inflammation that induces low oxygen levels, or hypoxia, is a widely accepted cause of cancer development. However, the link between hypoxia and cell proliferation is far from clear.

A new study by University of Georgia researchers presents a model explaining the connection between , low oxygen levels and the resulting cell proliferation that begins the process.

"A switch in energy metabolism mechanisms—from the normal oxygenic respiration our cells use to process glucose into energy to a much less efficient, much lower capacity process called anaerobic fermentation—leads to glucose accumulation," said Ying Xu, a Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the UGA Franklin College of Arts and Sciences.

According to the study, this accumulation of glucose and related signaling through the body leads to a reaction much the same as to that of damaged tissue, eventually triggering the cell proliferation that causes cancer. Specifically it leads to synthesis, export and fragmentation of hyaluronic acids, which can serve as signals for tissue repair. The study was published in the online edition of the International Journal of Cancer.

This new research builds on previously published studies authored by Xu's research group establishing low oxygen levels as a primary cause of uncontrollable tumor growth in some cancers.

Consensus thinking on the causes of cancer has centered on genetic mutations, Xu said. But by using gene expression data collected from cancer tissue rather than cancer cell lines, as often used in experimental cancer studies, bioinformatics has enabled researchers broader insight into the metabolic driver as well as key facilitator for cancer initiation that could have great impact on treatment regimes for malignant .

"When you compare statistics like the percentage of cured patients today versus 40 years ago, we can cure more cancer patients, though the primary reason is improvements in early detection," Xu said. "Cancer in its early stages is easier to treat, easier to control."

The focus on chronic inflammation, hypoxia and cell proliferation grew out of a need to understand the conditions connecting the three and why the body allows the growth of cancer cells in much the same way it repairs seemingly healthy cells. This led Xu to compare human tissue with that from a group of organisms that do not develop cancer. This group, including mammals (naked mole rat), as well as amphibians (frogs) and reptiles (turtles), shares an ability to survive in both aerobic and anaerobic environments. They are able to regulate their energy metabolisms according to oxygen availability, an ability to regulate energy demand according to supply never developed by humans.

"When the energy supply drops, our systems do not know how to turn off the energy demand accordingly," Xu said. "So there is an energy gap under persistent hypoxia when we begin to take in excess glucose, which produces glucose accumulation."

The model in the study outlines how the switch of to a less efficient process leads to increased glucose uptake within the cell. This glucose accumulation triggers the synthesis of hyaluronic acid, fragments of which outside the cell become signals for tissue injury and repair, leading to cell proliferation and angiogenesis, which starts the process of continuous —the very initial stage of the cancer process.

"It's a completely logical reaction from within our bodies, and our system is triggered to believe that the tissue is damaged," Xu said. "Cancer begins as a normal, if mistaken, mechanism for cell survival."

The study presents a fundamental reimagining of how cancer begins and could provide the basis for complete rethinking of cancer treatments, especially for late-stage cancer drugs.

"Given my research career as a cancer biologist, I am particularly excited to see this important advance by Dr. Xu and his colleagues," said David Lee, vice president for research at UGA. "The work points to fundamental metabolic changes that may be the primary cause of cancer in multiple tissues. If corroborated by further studies, it could suggest new approaches to cancer prevention and treatment."

More information: The study is available online:… 75&ArticleID=1323464

Related Stories

Low oxygen levels could drive cancer growth

date May 03, 2012

Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors' findings run counter to widely accepted beliefs that genetic mutations ...

Recommended for you

Spicy treatment the answer to aggressive cancer?

date Jul 03, 2015

It has been treasured by food lovers for thousands of years for its rich golden colour, peppery flavour and mustardy aroma…and now turmeric may also have a role in fighting cancer.

Cancer survivors who smoke perceive less risk from tobacco

date Jul 02, 2015

Cancer survivors who smoke report fewer negative opinions about smoking, have more barriers to quitting, and are around other smokers more often than survivors who had quit before or after their diagnosis, according to a ...

Melanoma mutation rewires cell metabolism

date Jul 02, 2015

A mutation found in most melanomas rewires cancer cells' metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.